Evidence of Band Bending Induced by Hole Trapping at MAPbI3 Perovskite / Metal Interface

International audienceElectron injection by tunneling from a gold electrode and hole transport properties in polycrystalline MAPbI3 has been investigated using variable temperature experiments and numerical simulations. The presence of a large and unexpected band bending at the Au/MAPbI3 interface is revealed and attributed to the trapping of holes, which enhances the injection of electrons via tunneling. These results elucidate the role of volume and interface defects in state-of-the-art hybrid perovskite semiconductors

Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction

High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI).; Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters.; Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu).; Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation.; NCT00470587, http://clinicaltrials.gov/show/NCT00470587

Direct comparison of BNP and NT-proBNP for mortality prediction in patients with acute dyspnea

Abstract Background It is unclear whether BNP or NT-proBNP, their admission or discharge measurement or percentage change during hospitalization are preferable for mortality prediction in patients with acute dyspnea. Purpose To directly compare BNP and NT-proBNP regarding their potential in mortality prediction in patients with acute dyspnea and in patients with dyspnea due to AHF. Methods In a prospective multicenter diagnostic study the presence of AHF was centrally adjudicated by two independent cardiologists among patients presenting with acute dyspnea. The levels of BNP and NT-proBNP were measured at presentation and discharge. Patients were stratified according to their natriuretic peptide response (responders vs. non-responders: natriuretic peptide decrease ≥25% vs. &amp;lt;25% before discharge). Prognostic accuracy for 720-day mortality was quantified using the area under the receiver-operating-characteristic curve (AUC). Cox proportional hazard models were constructed to identify significant predictors for 720-day mortality. Results Among 1156 patients presenting with acute dyspnea, 353 (30.5%) died within 720 days of follow-up. Prognostic accuracy for death at 720 days was significantly higher for discharge compared to admission measurements for BNP (AUC 0.750 vs. 0.711, p&amp;lt;0.001) and NT-proBNP (AUC 0.769 vs. 0.720, p&amp;lt;0.001). When directly comparing discharge measurements, NT-proBNP levels exhibited a significantly higher accuracy (p=0.013). 632 (54.6%) and 600 (51.9%) patients were BNP and NT-proBNP non-responders, respectively. Among BNP and NT-proBNP non-responders 202 (32%) and 207 (34.5%) patients died within 720 days of follow-up. After adjusting for common covariates NTproBNP response was the strongest predictor for 720-day mortality in a Cox regression model (Hazard ratio for NT-proBNP non-responders: 2.096 (95% CI 1.550–2.835), p&amp;lt;0.001). Results were confirmed in a sensitivity analysis of 687 (59.4%) patients with adjudicated AHF. Conclusion Percentage change of NT-proBNP during hospitalization seems to be the strongest predictor for long-term mortality in patients with acute dyspnea in general and in those with dyspnea due to AHF in particular. ROC curve for direct comparison Funding Acknowledgement Type of funding source: None </jats:sec

P3532Quantifying hemodynamic cardiac stress and cardiomyocyte injury in hypertensive and normotensive acute heart failure

Abstract Background Better characterization of the different pathophysiological mechanisms involved in normotensive and hypertensive acute heart failure (AHF) might help to develop novel individualized treatment strategies. Methods The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring B-type natriuretic peptide (BNP) as well as high-sensitive cardiac troponin T (hs-cTnT) in 1,152 unselected patients presenting with AHF to the emergency department (derivation cohort). Systolic blood pressure (SBP) of 90 - 140 mmHg at presentation was used to define normotensive AHF. Findings regarding hemodynamic cardiac stress and cardiomyocyte injury were validated in a second independent AHF cohort (validation cohort; n=324). Results In the derivation cohort 667 (58%) patients had hypertensive AHF. Hemodynamic cardiac stress, as quantified by BNP levels, was significantly higher in normotensive AHF as compared to hypertensive AHF (1,105 pg/mL versus 827 pg/mL, p&lt;0.001). In addition, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF (41 ng/L versus 33 ng/L, p&lt;0.001). These findings were confirmed in the validation cohort. Table 1. Cardiac stress and myocardial necrosis as quantified by BNP and hs-cTnT plasma concentrations Overall Hypertensive AHF Normotensive AHF p-value BNP in pg/ml, median (IQR) 974 (536–1,712) 827 (448–1,419) 1,105 (611–1,956) &lt;0.001 hs-cTnT in ng/L, median (IQR) 37 (22–67) 33 (19–59) 41 (24–71) &lt;0.001 BNP = B-type natriuretic peptide; hs-cTnT = high-sensitivity cardiac Troponin T; IQR = inter-quartile range. Figure 1 Conclusion Biomarker profiling revealed that the extent of hemodynamic stress and cardiomyocyte injury is different in patients with normotensive and hypertensive AHF. This characterization could help to understand AHF phenotypes better, which in turn may lead to more specific management in future, thus improving the dismal prognosis in these patients. Acknowledgement/Funding European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel </jats:sec

P792Cardiac myosin-binding protein C for the diagnosis and long-term prognosis of acute heart failure

Abstract Background Cardiac myosin-binding protein C (cMyC) is a novel biomarker quantifying cardiac injury. Its utility for the diagnosis, prognosis, and therapy guidance in acute heart failure (AHF) is unclear. Methods In a prospective diagnostic multicentre study, unselected patients presenting with acute dyspnoea to the emergency department were enrolled. cMyC, high-sensitive cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations were measured. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient's information. Co-primary outcome measures were cMyC's: diagnostic safety and efficacy; prognostic accuracy. Results Among 1,330 recruited patients, 247 from an AHF substudy were not included in the diagnostic analysis. Accordingly, 548 patients (51%) in this analysis had an adjudicated diagnosis of AHF. For the rapid rule-out of AHF, the cMyC cut-off concentration at 16 ng/L achieved a sensitivity of 95% (95% CI, 93–97%), a negative predictive value of 88% (95% CI, 84–92%), and allowed to rule-out 21% of the patients. Correspondingly, cMyC's efficacy and safety in the triage of AHF were slightly lower than NT-proBNP's. Of the 790 AHF patients in the prognostic analysis, 222 (28%) died during the 360 days' follow-up. Patients with cMyC plasma concentrations above the median had significantly shorter mean time to death (274 versus 320 days, p=0.001). Compared to hs-cTnT and discharge NT-proBNP, cMyC showed non-inferior prognostic accuracy. No significant interactions between cMyC and cardiac medical therapies at discharge in predicting 360 days survival were present. Conclusion cMyC performs well in the rapid triage and prognosis of AHF. Acknowledgement/Funding European Union, Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University Hospital of Basel </jats:sec

P785Unplanned readmissions after discharge increases risk of death in acute dyspnoea patients: non-cardiac is as severe as cardiac causes

Abstract Introduction Acute dyspnoea is a major reason for admission to the emergency department and has been associated with high rates of readmission and mortality. However, the association of readmission with mortality risk has not been widely studied in patients with acute dyspnoea. Purpose To determine whether unplanned readmission during first 6 months after discharge is associated with greater risk of death within 1 year in patients with acute dyspnoea. Methods Derivation cohort consisted of 1371 patients from the prospective observational study, which enrolled acute dyspnoea patients admitted to emergency departments of two university centres from 2015 to 2017 and discharged alive from the hospital. Cox regression analysis compared 1-year risk of death between readmitted vs. non-readmitted patients in the first 6 months after discharge. In addition, we studied this association in 1986 patients from a multicentre validation cohort, which included acute dyspnoea patients from 2006 to 2014. Sensitivity analysis was done in the subgroups divided by cause of index admission (acute heart failure [AHF] and non-AHF) and cause of the first readmission (cardiovascular [CV] or non-CV). The statistical analyses were performed using R statistical software. P value of &lt;0.05 was considered statistically significant. Results In the derivation cohort 666 (49%) of patients were readmitted at 6 months and 282 (21%) died in 1 year. Readmitted patients died more frequently than non-readmitted patients (211 [32%] vs. 71 [10%], respectively, p&lt;0.001). All-cause 6-month readmission was associated with an increased 1-year risk of death in a multivariate analysis in both the derivation cohort (adjusted hazard ratio (aHR) 3 [95% confidence interval (CI) 2.2–4], p&lt;0.001) and the validation cohort (aHR 1.8 [95% CI 1.4–2.2], p&lt;0.001). Moreover, deleterious effect of readmission on 1-year survival was equally observed in AHF and non-AHF patients, independent of whether the reason of first readmission was cardiovascular or non-CV, in both study cohorts. The results are displayed in Figure 1. Figure 1. Main results of the study Conclusions Our data demonstrates that readmission is associated with a markedly increased risk of death within 1 year in patients presenting to the emergency department with acute dyspnoea. Furthermore, the detrimental relationship between outcomes is similar in non-cardiac and cardiac causes. Acknowledgement/Funding The work was supported by the Research Council of Lithuania, grant Nr. MIP-049/2015 and approved by Lithuanian Bioethics Committee, Nr. L-15-01. </jats:sec

Quantifying inflammation using interleukin-6 for improved phenotyping and risk stratification in acute heart failure

Abstract Background Acute heart failure (AHF) is the most common cause of hospital admission and continues to have unacceptable high rates of mortality and morbidity. In contrast to acute myocardial infarction, the pathophysiology of AHF is incompletely understood and risk-prediction is poorly defined. Aim We aimed to quantify systemic inflammation to assess its possible role in the pathophysiology and risk stratification of patients with AHF. Methods Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01ng/l) we quantified systemic inflammation in unselected patients presenting with acute dyspnea to the emergency department in a multicenter study. Plasma concentrations of NT-proBNP (open label) and Interleukin-6 (blinded) were measured at presentation and at discharge. The final diagnosis of AHF and the AHF phenotype were adjudicated by two independent cardiologists. 1-year mortality was the prognostic endpoint. Results Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF. Interleukin-6 concentrations were significantly higher in AHF patients compared to patients with other causes of dyspnoea (11.2 [6.1–26.5] ng/l vs 9.0 [3.2–32.3] ng/l, p&amp;lt;0.0005). Among patients with AHF Interleukin-6 concentrations were elevated (&amp;gt;4.45ng/l) in 83.7% of them. Among the different AHF phenotypes, Interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0–164.2] ng/l) and lowest in patients with hypertensive HF (9.3 [4.8–21.6] ng/l, p=0.001). Inflammation as quantified by Interleukin-6 was a strong predictor of 1-year mortality both in AHF as well as in other causes of acute dyspnea (Figure). During in-hospital treatment Interleukin-6 concentrations significantly decreased in AHF patients. However, changes in the extend of systemic inflammation (delta Interleukin-6) were poorly correlated with changes in hemodynamic stress as quantified by NT-proBNP (delta NT-proBNP, Φc=0.11, p=0.004). Conclusions An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation that can be quantified by Interleukin-6, which seems to contribute to the AHF phenotype and to the risk of death. Kaplan Meier curves for mortality Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation, European Union, Stiftung für kardiovaskuläre Forschung Basel, University of Basel, University Hospital Basel </jats:sec

P2617Activity of the adrenomedullin system to personalize post-discharge treatment in acute heart failure

Abstract Objectives Activity of the adrenomedullin system was quantified by using bioactive-adrenomedullin (bio-ADM), the biologically active moiety, and midregional proadrenomedullin (MR-proADM), a prohormone fragment, to 1) identify acute heart failure (AHF) phenotypes with disproportional benefit or harm from specific treatments at hospital discharge, 2) predict mortality, and 3) compare the prognostic utility of both biomarkers. Methods This prospective multicentre study using central adjudication of AHF measured bio-ADM in all patients and MR-proADM in a predefined subgroup in a blinded fashion on admission. Both biomarkers were measured at discharge as well. Interaction with specific treatments at hospital discharge and the biomarkers' prognostic utility during 365 days' follow-up were assessed. Results Among 1,886 patients with adjudicated AHF, 514 patients (27.3%) died during the 365 days' follow-up. Patients with bio-ADM plasma concentrations above the median were at a much higher risk of death (HR 1.87, 95% CI 1.57–2.24; p&lt;0.001). After adjusting for age, creatinine plasma concentrations, and medical treatment at discharge, those patients derived disproportional benefit if treated with diuretics and/or angiotensin-converting-enzyme inhibitors/angiotensin receptor blocker (interaction p-values &lt;0.05). These findings were confirmed only for the diuretics treatment when quantifying the adrenomedullin system using MR-proADM plasma concentrations (n=764). For predicting mortality, both biomarkers performed well and MR-proADM had a higher predictive accuracy as compared to bio-ADM (p&lt;0.001). Table 1. Interaction p-values in multivariate models using a cox proportional hazard analysis for predicting all-cause mortality at 365 days including age, bio-ADM or MR-proADM, creatinine at discharge, and medication at discharge Diuretics ACE inhibitors or ARB Beta blockers Aldosterone antagonists lg bio-ADM*, ng/l &lt;0.001 0.011 0.760 0.175 lg bio-ADM†, ng/l &lt;0.001 0.020 0.807 0.396 lg MR-proADM*, nmol/l 0.031 0.095 0.169 0.441 lg MR-proADM†, nmol/l 0.001 0.126 0.741 0.272 *At admission; †at discharge. ACE: Angiotensin-converting-enzyme; ARBs: Angiotensin receptor blocker; bio-ADM: bioactive adrenomedullin; MR-proADM: midregional proadrenomedullin. Figure 1 Conclusion Quantifying the activity of the adrenomedullin system helps to personalize post-discharge treatment and risk-prediction in AHF. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, University of Base, Sphingotec </jats:sec

Early standardized clinical judgement for syncope diagnosis in the emergency department

The diagnosis of cardiac syncope remains a challenge in the emergency department (ED).; Assessing the diagnostic accuracy of the early standardized clinical judgement (ESCJ) including a standardized syncope-specific case report form (CRF) in comparison with a recommended multivariable diagnostic score.; In a prospective international observational multicentre study, diagnostic accuracy for cardiac syncope of ESCJ by the ED physician amongst patients ≥ 40 years presenting with syncope to the ED was directly compared with that of the Evaluation of Guidelines in Syncope Study (EGSYS) diagnostic score. Cardiac syncope was centrally adjudicated independently of the ESCJ or conducted workup by two ED specialists based on all information available up to 1-year follow-up. Secondary aims included direct comparison with high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) concentrations and a Lasso regression to identify variables contributing most to ESCJ.; Cardiac syncope was adjudicated in 252/1494 patients (15.2%). The diagnostic accuracy of ESCJ for cardiac syncope as quantified by the area under the curve (AUC) was 0.87 (95% CI: 0.84-0.89), and higher compared with the EGSYS diagnostic score (0.73 (95% CI: 0.70-0.76)), hs-cTnI (0.77 (95% CI: 0.73-0.80)) and BNP (0.77 (95% CI: 0.74-0.80)), all P < 0.001. Both biomarkers (alone or in combination) on top of the ESCJ significantly improved diagnostic accuracy.; ESCJ including a standardized syncope-specific CRF has very high diagnostic accuracy and outperforms the EGSYS score, hs-cTnI and BNP